Charleston Laboratories, Inc. and Daiichi Sankyo, Inc. Announce FDA Acceptance of New Drug Application (NDA) for CL-108

In continuation of my updates on hydrocodone, Promethazine & acetaminophen

Charleston Laboratories, Inc. and Daiichi Sankyo, Inc.  announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for CL-108   (is a novel bi-layered tablet containing 12.5mg of immediate release promethazine with a modified release of 7.5 mg of hydrocodone and 325mg of acetaminophen) for the relief of moderate to severe pain while preventing or reducing the associated opioid-induced nausea and vomiting (OINV). CL-108 is a fixed-dose, immediate-release bi-layered tablet with a rapid release layer containing 12.5 mg of promethazine and a second layer containing 7.5 mg of hydrocodone and 325 mg of acetaminophen. The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of January 31, 2017.

 promethazine

"With this NDA acceptance, patients are one step closer to being able to have an option for relieving pain while also preventing or minimizing the nausea and vomiting side effects of opioid treatment," said Paul Bosse, President and Chief Executive Officer of Charleston Laboratories, Inc. "At Charleston Laboratories, a key part of our mission is to develop and commercialize products that provide patients with novel solutions for improving their pain management. This acceptance represents an important contractual milestone under our relationship with Daiichi Sankyo."

"Daiichi Sankyo is dedicated to bringing innovative medicines to patients with unmet medical needs in the area of pain management," said Mahmoud Ghazzi, MD, PhD, President and Global Head of Development for Daiichi Sankyo. "We look forward to working closely with the FDA during the review process for CL-108 and support the Agency's efforts to foster the safe and responsible use of opioid medications."

The NDA for CL-108 is supported by two pivotal randomized, double-blind, placebo- and active-controlled Phase 3 clinical studies, one following oral surgery (molar removal) and the other after bunionectomy surgery (removal of bunions from the foot), as well as by an additional Phase 3 open-label, actual use safety study in patients with moderate-to-severe acute pain, or "flares," associated with osteoarthritis of the knee or hip. More than 1,000 patients have been enrolled in the CL-108 Phase 3 clinical trial program. A human abuse liability study has also been conducted.

New class of antidepressants appears potentially effective in combating deadly form of lung cancer

Jahchan tested the effect of a tricyclic antidepressant called imipramine  (see structure)  on human small-cell lung cancer cells grown in the laboratory and growing as tumors in laboratory mice. She found that the drug was able to potently activate a self-destruction pathway in the cancer cells and to slow or block metastases in the animals. The drug maintained its effectiveness regardless of whether the cancer cells had previously been exposed, and become resistant, to traditional chemotherapy treatments. Another drug, an antihistamine called promethazine, identified by the bioinformatics screen, also exhibited cancer-cell-killing abilities.

Although imipramine did not affect cells from another main type of lung cancer called non-small-cell lung adenocarcinoma, it did inhibit the growth of cells from other neuroendocrine tumors, including pancreatic neuroendocrine cancers, an aggressive skin cancer called Merkel cell carcinoma, and a pediatric cancer called neuroblastoma. (Neuroendocrine cells receive signals from the nervous system and secrete hormoneslike adrenaline into the blood to affect the body's function.)

Further investigation showed that the drugs appear to work through a class of molecule on the cancer cells' surfaces called G-protein-coupled receptors, but the researchers are continuing to investigate exactly how the drugs specifically kill neuroendocrine cancer cells.

"Our collaboration with the Butte lab allowed us to move very quickly from the initial idea to very convincing results," Sage said. "It was less than 20 months from the time of our first discussion to a clinical trial because the bioinformatics approach had been established and the drugs are FDA-approved. By focusing on diseases with little hope for the patient, it's easier to go forward fast."

Ref : http://cancerdiscovery.aacrjournals.org/content/early/2013/09/16/2159-8290.CD-13-0183.abstract

New class of antidepressants appears potentially effective in combating deadly form of lung cancer